The following questions and answers have been prepared by the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration. This guidance represents the Agency's current thinking on pediatric exclusivity (505A). It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations or both.

Issue Written Requests for pediatric studies prior to approval of a new drug application if FDA has determined that information related to the use of the drugs in the pediatric population may produce health benefits.

Issue Written Requests to holders of approved applications for pediatric studies if it has determined that information related to the use of the drug in the pediatric population may produce health benefits.

Section 505(A) also required FDA to develop, prioritize, and publish a list of approved drugs for which additional pediatric information may produce health benefits in the pediatric populations and update it annually.

As an incentive to industry to conduct studies requested by the Agency, Section 505(A) provides for a 6-month period of marketing exclusivity (pediatric exclusivity).

Q1.How does a sponsor or applicant qualify for pediatric exclusivity?

A1. Three essential elements must be in place before an applicant is eligible for pediatric exclusivity. To qualify for pediatric exclusivity, the applicant must meet all of the following conditions:

Be in receipt of a written request from FDA. On June 30, 1998, FDA issued a Guidance for Industry, Qualifying for Pediatric Exclusivity Under Section 505(A) if the Federal Food, Drug, and Cosmetic Act (June 1998) [PDF]. The guidance describes what constitutes a Written Request and what it must address. Prior correspondence with applicants regarding clinical trials, agreements at meetings, correspondence describing phase 4 commitments, and other communications with sponsors DO NOT CONSTITUTE a Written Request. The Written Request describes in detail the studies needed and the time frame for their completion; the guidance describes ways in which the Written Request can be amended to revise the study requirements or the specified time frame. The Written Request is the key to whether submitted study reports qualify the applicant for pediatric exclusivity.

Submit study reports after receipt of the written request. Firms are to submit reports of studies conducted in pediatric populations to the FDA after FDA has issued a Written Request. Under the terms of the statute, FDA must determine whether the studies submitted meet the terms of the Written Request. Submissions of reports should generally be in the form of a new drug application, a supplement to an approved application, or an amendment to a pending application. A firm should, but is not required to, obtain approval of pediatric labeling to qualify for pediatric exclusivity.

Meet the conditions of the written request. Whether an applicant qualifies for exclusivity for a product after conducting the studies and submitting the reports depends on whether:

- The submission meets the time frame described in the Written Request, and

- The studies performed meet the terms specified in the Written Request.

Q2.Can an applicant ask FDA to issue a Written Request for pediatric studies?

A2. Yes. The guidance to industry describes a process in which a sponsor of a new drug or the holder of an application for a product on the list may make a submission to FDA in which it makes a detailed proposal for a Written Request. Where an applicant has more than one product containing the active moiety, the proposal should address each indication that has applicability to pediatric patients and should propose studies in all appropriate age groups. FDA encourages applicants to make such proposals. FDA will review the submitted proposal and MAY issue a Written Request to the applicant based on the applicant's proposal.

Q3.Where should proposals for Written Requests from applicants be sent?

A3. Proposals for Written Requests should be sent to each of the review divisions with regulatory responsibility for any of the applicant's products that contains the same active moiety cited in the Written Request.

Q4. Does a sponsor HAVE to conduct pediatric studies if it receives a Written Request from FDA?

A4. No. A company is not required to do the studies requested by FDA in a Written Request if it chooses not to do so. If, however, the applicant decides to conduct studies that differ from those described in the Written Request, the applicant will not qualify for pediatric exclusivity upon submission of the reports thereof. Applicants who choose to deviate from the studies described in the Written Request and who are interested in obtaining pediatric exclusivity should contact the review division and seek to amend the Written Request prior to the conduct of the studies. The applicant must receive an amended Written Request prior to submission of the study reports to NDA.

Q5.Can an applicant obtain exclusivity by submitting an analysis of the literature in response to a Written Request?

A5. Simply compiling the literature on pediatric use of a drug in a given indication will not qualify an applicant for pediatric exclusivity. The generous incentives were made available to stimulate performance of studies necessary to provide useful information on drug use in children.

Q6. Can the applicant for any approved product qualify for pediatric exclusivity?

A6. No. Pediatric exclusivity is an ADD-ON to existing marketing exclusivity or patent protection. In general, products with no patent life or exclusivity remaining cannot qualify. Under certain conditions, however, pediatric exclusivity may be granted to a product without remaining exclusivity IF the supplemental application itself qualifies for a new exclusivity period under the Drug Price Competition and Patent Term Restoration Act (Waxman-Hatch Amendments). For example, an application to extend an approved adult indication to the pediatric population for a product with no patent life or exclusivity remaining could obtain pediatric exclusivity IF new clinical studies of safety and efficacy are required for approval. In that case, the pediatric supplement would earn 3 years of marketing exclusivity under the 1984 amendments, to which the additional 6 month pediatric exclusivity would be added. A somewhat different situation would be where dosing information was needed in children under 6 years of age that could be based on PK studies. An oral solution dosage form exists but has no marketing exclusivity remaining. However, the firm has a controlled release product containing the same active moiety that is still protected by a 3 year exclusivity period. The controlled release product would not be appropriate for this age group because of the dose delivered. In this situation, PK studies conducted to label the oral solution could be the basis of a 6 month extension of the exclusivity for the controlled release product, provided the terms of the Written Request are met.

Q7. Does Section 505(A) apply to OTC drugs?

A7. Yes. It applies to those OTC drugs that are the subject of approved NDAs.

Q8. For approved drugs, must FDA approve a supplemental application before pediatric exclusivity is granted?

A8. No. The granting of exclusivity is not connected to approval; the pivotal factor is whether the applicant complied with the terms of the Written Request.

Q9. How is pediatric exclusivity different from other exclusivity available under the Waxman-Hatch amendments or the Orphan Drug Act?

A9. Pediatric exclusivity differs from other exclusivity in the following important ways:

Pediatric exclusivity does not accrue only to the product that was studied in the pediatric population. It attaches to all the applicant's formulations, dosage forms, and indications for products with existing marketing exclusivity or patent life that contain the same active moiety. For example, if a firm markets an oral formulation, a topical cream, and an ophthalmic containing the same active moiety and all the products have remaining marketing exclusivity or patent life, and if the firm conducts studies regarding the active moiety in accordance with a Written Request, 6 months additional exclusivity will be granted to ALL DOSAGE FORMS AND ALL INDICATIONS with the same active moiety as the drug studied.

Pediatric exclusivity attaches to the END of all existing marketing exclusivity and patent periods. Waxman-Hatch exclusivity, orphan exclusivity, and patent periods run concurrently.

Pediatric exclusivity is not tied to approval of labeling containing information on pediatric use based on the studies conducted. It may be granted upon acceptance of the study reports. Acceptance in this context means the Agency has determined that the studies were conducted in accordance with the terms of the Written Request and were reported in accordance with FDA's requirements for filing. Waxman-Hatch and orphan exclusivity are not granted until approval of the application.

Q10. Should a Written Request be issued to the IND or NDA holder?

A10. If an NDA for the drug product exists, the Written Request should be issued to the applicant of the NDA. If no NDA exists for the product, the Written Request should be issued to the IND holder.

Q11. For over-the-counter (OTC) products that are the subject of an NDA, which Office Director should sign Written Requests for pediatric studies?

A11. Consistent with CDER policy for decision making responsibilities on certain other regulatory documents that require Office level sign-off pertaining to OTC drug products subject to NDAs, both the Director of ODE V and the Director of the Office responsible for the specific subject matter review division should sign Written Requests for OTC products.

Q12. Where can I get answers to questions that come up regarding our implementation of the pediatric exclusivity provisions?

A12 Send questions via E-mail to pdit@cder.fda.gov. It is an E-mail account that has been set up by the Pediatric Implementation Team.